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Objectives: This study aimed to determine possible associations between transcriptional and translational levels of clusterin (CLU) in the systemic and local joint environments with the severity of knee osteoarthritis (OA) and to investigate CLU mRNA expression in knee OA fibroblast-like synoviocytes (FLSs) stimulated with tumor necrosis factor-α., Design: Circulating and synovial fluid CLU levels in 259 knee OA patients were quantified using an enzyme-linked immunosorbent assay. Relative CLU mRNA expression in 50 knee OA synovial tissues and 4 knee OA FLSs was determined using real-time polymerase chain reaction., Results: Plasma CLU levels of knee OA patients were significantly higher than paired synovial fluid samples. Compared with early-stage knee OA patients, those with advanced-stage OA had considerably increased plasma and synovial fluid CLU levels. There were significant positive associations of plasma and synovial fluid CLU levels with radiographic severity of knee OA. Plasma CLU levels were directly correlated with its synovial fluid levels and high-sensitivity C-reactive protein levels in the patients. Receiver-operating characteristic curve analysis unveiled the potential utility of plasma CLU as a novel biomarker for knee OA severity (AUC = 0.80), with a sensitivity of 71.4% and a specificity of 73.3%. Marked upregulation of CLU mRNA expression was observed in both the inflamed synovial tissues and FLSs of knee OA., Conclusion: Increased CLU mRNA and protein levels in the systemic and local joint environments of knee OA might reflect knee OA severity, especially systemic and synovial inflammation.

Objective: Glypican-3 possesses a possible action in regulation of bone growth and development implicated in osteoarthritis (OA) pathology. Therefore, this study aimed to investigate glypican-3 in plasma and synovial fluid of knee OA patients and to determine the possible association between glypican-3 levels and radiographic severity., Design: A total of 80 knee OA patients and 80 healthy controls were recruited. Glypican-3 levels in plasma and synovial fluid were measured using enzyme-linked immunosorbent assay. The severity of knee OA was assessed by radiographic grading according to the Kellgren-Lawrence classification. Relative mRNA expression of glypican-3 in 10 inflamed synovial tissues from OA patients and 10 noninflamed synovial controls was quantified using real-time polymerase chain reaction., Results: Plasma glypican-3 levels were significantly lower in OA patients than in healthy controls ( P = 0.03), whereas synovial fluid glypican-3 levels were remarkably greater than in paired plasma samples of OA patients ( P < 0.001). Subsequent analysis demonstrated that plasma and synovial fluid glypican-3 levels were inversely associated with the radiographic severity of knee OA ( r = -0.691, P < 0.001; r = -0.646, P < 0.001, respectively). Furthermore, there was a positive relationship between plasma and synovial fluid glypican-3 levels in knee OA patients ( r = 0.515, P < 0.001). Additionally, overexpression of glypican-3 mRNA was observed in inflamed synovium of OA patients ( P = 0.021)., Conclusions: The present study revealed that plasma and synovial glypican-3 levels were negatively associated with radiographic severity of knee OA. Glypican-3 could emerge as a potential biomarker for reflecting the severity of knee OA and might play a plausible role in the pathophysiology of degenerative joint disease.

Objective: Heat shock proteins are molecules rapidly produced under conditions of environmental stress, and involve in protecting the cells structural integrity and function. Osteoarthritis (OA) is a chronic destructive disorder of the joints manifested by the ongoing deterioration and loss of articular cartilage. The present study aimed to analyze circulating and synovial heat shock protein (Hsp70) values in knee osteoarthritis patients and healthy controls and to determine their relationship with the radiographic grading of the severity of knee OA., Design: Seventy-two subjects with knee OA and 30 control participants were recruited. Circulating and joint fluid Hsp70 values were quantified by commercially available enzyme-linked immunosorbent assay., Results: Circulating Hsp70 was markedly higher in knee OA patients compared with that of healthy volunteers ( P = 0.01). Correspondingly, synovial fluid Hsp70 was 3-fold greater than paired circulating Hsp70 samples ( P < 0.001). Further analysis revealed that circulating and joint fluid Hsp70 values were significantly related with the radiographic severity of knee OA ( r = 0.413, P < 0.001 and r = 0.658, P < 0.001, respectively). Subsequently, circulating Hsp70 value was directly associated with joint fluid Hsp70 value ( r = 0.704, P < 0.001)., Conclusions: Circulating and synovial Hsp70 levels were positively correlated with the radiographic severity of knee OA. Hsp70 could represent a potential biochemical marker for predicting the severity and may play a fundamental part in the pathogenic mechanism of knee OA.

Objective: The objective of this study is to compare inflammatory cytokine levels in primary knee osteoarthritis (OA) patients and healthy controls., Methods: A total of 32 knee OA patients and 14 healthy controls were enrolled. A multiplex immunoassay was utilized for 10 cytokines in plasma and synovial fluid., Results: Plasma IL-2, IL-4, and IL-6 concentrations were significantly greater in knee OA patients than controls. Moreover, both plasma IL-4 and IL-6 were positively correlated with the radiographic severity of knee OA., Conclusions: Plasma IL-4 and IL-6 may serve as biomarkers reflecting the severity of OA.

Objective: To investigate plasma and synovial fluid (SF) periostin of knee osteoarthritis (OA) patients and to determine the relationship between periostin levels and the radiographic severity., Methods: A total of 110 subjects (90 knee OA patients and 20 healthy controls) were enrolled in this study. Plasma and SF periostin were examined using an enzyme-linked immunosorbent assay. OA grading was performed using the Kellgren-Lawrence classification., Results: Although plasma periostin was greater in OA patients than in controls, the difference was not significant. Additionally, SF periostin was significantly higher with respect to paired plasma (P<0.001). Moreover, plasma and SF periostin demonstrated significantly positive correlation with the radiographic severity of knee OA (r=0.537, P<0.001 and r=0.427, P<0.001, respectively). Subsequent analysis revealed that there was a positive correlation between plasma and SF periostin (r=0.368, P<0.001)., Conclusions: Plasma and SF periostin levels were positively correlated with the radiographic severity of knee OA., (Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Background: This study aimed to investigate the relationships between plasma and synovial autotaxin and the severity in knee osteoarthritis (OA) patients., Methods: A total of 90 participants (70 knee OA patients and 20 controls) were recruited. Autotaxin and high-sensitivity C-reactive protein (hs-CRP) levels were determined. The symptomatic and radiographic severity of OA was assessed using the Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores and the Kellgren-Lawrence grades., Results: OA patients had significantly higher circulating autotaxin and hs-CRP than controls. Plasma autotaxin was directly correlated with synovial fluid autotaxin (r=0.639, P<0.001). Additionally, plasma and synovial fluid autotaxin were associated with radiographic severity (P<0.001). Furthermore, plasma and synovial fluid autotaxin levels were positively correlated with WOMAC scores (r=0.558, P<0.001 and r=0.371, P=0.002, respectively)., Conclusion: Plasma and synovial fluid autotaxin levels were positively correlated with the severity of OA. Thus, autotaxin has potential as a biomarker reflecting the severity of knee OA., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: The aim of this study was to compare angiogenic cytokine levels in knee osteoarthritis (OA) patients and healthy controls and to investigate the relationships between angiogenic cytokines and the OA severity., Methods: Thirty-one knee OA patients and 15 healthy controls were recruited. Nine angiogenic cytokines (angiopoietin-2, follistatin, granulocyte-colony stimulating factor (G-CSF), hepatocyte growth factor (HGF), interleukin (IL)-8, leptin, platelet-derived growth factor-BB (PDGF-BB), platelet endothelial cell adhesion molecule (PECAM)-1, and vascular endothelial growth factor (VEGF)) in plasma and synovial fluid were measured using a multiplex immunoassay., Results: PECAM-1, HGF, VEGF, angiopoietin-2, follistatin, G-CSF, and IL-8 concentrations in plasma were significantly higher in OA patients than those in controls. Plasma angiopoietin-2 was significantly greater in advanced OA than in early OA. Synovial fluid VEGF was positively correlated with the severity (r = 0.367, P = 0.04). Plasma follistatin was significantly lower in advanced knee OA than in early OA and was negatively correlated with the severity (r = -0.374, P < 0.05)., Conclusions: Angiogenic cytokine concentrations in plasma can distinguish between controls and OA patients. Local and circulating levels of angiogenic cytokines could give an insight into the pathophysiology of OA. Follistatin, angiopoietin-2, and VEGF may have potential as biochemical markers for the assessment of OA severity.

Objective: The purpose of this study was to analyze sclerostin in plasma and synovial fluid of knee osteoarthritis (OA) patients and to investigate the association between sclerostin levels and radiographic severity., Design and Methods: A total of 190 subjects (95 knee OA patients and 95 healthy controls) were recruited in the present study. Sclerostin levels in plasma and synovial fluid were assessed using an enzyme-linked immunosorbent assay. OA grading was performed using the Kellgren-Lawrence classification., Results: Plasma sclerostin levels were significantly lower in OA patients than in healthy controls (P=0.004). Additionally, sclerostin levels in plasma were significantly higher with respect to paired synovial fluid (P<0.001). Moreover, sclerostin levels in plasma and synovial fluid demonstrated a significant inverse correlation with the radiographic severity of knee OA (r=-0.464, P<0.001 and r=-0.592, P<0.001, respectively). Subsequent analysis revealed that there was a positive correlation between plasma and synovial sclerostin levels (r=0.657, P<0.001)., Conclusions: Sclerostin was significantly lower in OA plasma samples when compared with healthy controls. Plasma and synovial fluid sclerostin levels were inversely associated with the radiographic severity of knee OA. Therefore, sclerostin may be utilized as a biochemical marker for reflecting disease severity in primary knee OA., (Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Purpose: Recent evidence suggests that angiogenesis and inflammation contribute to the development and progression of osteoarthritis (OA). The purpose of this study was to investigate vascular endothelial growth factor (VEGF) levels in plasma and synovial fluid of patients with knee OA and to determine the relationship of VEGF levels with disease severity in knee OA., Methods: A total of 100 subjects were enrolled in this study (80 knee OA patients and 20 healthy controls). Plasma and synovial fluid VEGF levels were analysed using enzyme-linked immunosorbent assay. VEGF expressions in synovial membrane and articular cartilage samples were assessed using immunohistochemistry., Results: VEGF level in synovial fluid of knee OA patients was tenfold higher than that in paired plasma (P < 0.001). Both plasma and synovial fluid VEGF exhibited a positive correlation with radiographic severity (r = 0.454 and r = 0.727, P < 0.001, respectively). VEGF expression was highly detectable in synovial lining cells and articular chondrocytes of knee OA patients., Conclusions: VEGF levels in both plasma and synovial fluid were positively correlated with the severity of knee OA. Therefore, VEGF may be useful for monitoring OA severity and could play a substantial role in the development and progression of knee OA.

Background: Connective tissue growth factor (CTGF) has been implicated in development of osteoarthritis (OA)., Objective: To determine the correlation between plasma and synovial fluid CTGF levels and the severity in knee osteoarthritis patients., Methods: A total of 100 subjects were recruited into this study (75 OA patients and 25 controls). CTGF concentrations in plasma and synovial fluid were analyzed by enzyme-linked immunosorbent assay., Results: Plasma and synovial fluid CTGF concentrations were correlated with radiographic severity. There was a positive correlation between plasma and synovial fluid CTGF levels., Conclusion: CTGF could be useful for monitoring the severity and progression of OA.

Purpose: The aim of this study was to investigate plasma and synovial fluid basic fibroblast growth factor (bFGF) levels in patients with primary knee osteoarthritis (OA) and to evaluate the correlation between bFGF levels and disease severity., Methods: Thirty-five patients with knee OA and 15 healthy individuals were recruited into this study. Knee OA grading was performed according to the Kellgren-Lawrence classification. bFGF concentrations in both plasma and synovial fluid were determined using enzyme-linked immunosorbent assay., Results: Plasma and synovial fluid bFGF levels in knee OA patients were significantly higher than in controls (P < 0.001). Moreover, plasma and synovial fluid bFGF concentrations were positively correlated with radiographic severity (r = 0.535, P < 0.001 and r = 0.570, P < 0.001, respectively). Further analysis revealed that there was a positive correlation between plasma and synovial fluid bFGF levels (r = 0.674, P < 0.001)., Conclusions: Plasma and synovial fluid bFGF levels were significantly increased in OA patients, and these elevated levels were positively correlated with radiographic severity. These findings indicate that bFGF levels may be a monitor of disease severity and could play an essential part in the pathophysiology of degenerative process in OA.

Objectives: The objective of this study was to investigate interferon-γ inducible protein-10 (IP-10) concentrations in plasma and synovial fluid of patients with knee osteoarthritis (OA) and to analyze their relationship with disease severity., Design and Methods: Forty OA patients and 15 healthy controls were enrolled in this study. OA grading was performed according to the Kellgren-Lawrence criteria. IP-10 levels in plasma and synovial fluid were assessed using enzyme-linked immunosorbent assay., Results: Plasma IP-10 levels in the knee OA patients were significantly lower than those of controls (P=0.006). IP-10 levels in plasma were markedly higher with regard to paired synovial fluid (P<0.001). Furthermore, IP-10 concentrations in plasma and synovial fluid displayed significant inverse correlation with radiographic severity (r=-0.713, P<0.001 and r=-0.561, P<0.001, respectively). Subsequent analysis revealed that plasma IP-10 levels were positively correlated with synovial fluid IP-10 levels (r=0.424, P=0.006)., Conclusions: IP-10 levels in both plasma and synovial fluid were inversely associated with the severity of knee OA. Accordingly, IP-10 could serve as a biomarker for determining disease severity and might play a possible role in the pathophysiology of osteoarthritis., (Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Osteoarthritis (OA) is a common degenerative joint disease causing pain, stiffness, reduced motion, swelling, crepitus, and disability. Dickkopf-1 (Dkk-1) is a critical mediator of osteoblastogenesis and regulates the joint remodeling. The aim of this study was to examine plasma and synovial fluid Dkk-1 levels of patients with primary knee OA and to investigate their relationship with disease severity., Methods: Thirty-five patients aged 55-83 years with knee OA and 15 healthy individuals were recruited into this study. Disease severity was determined using weight-bearing anteroposterior radiographs of the affected knee. The radiological grading of OA in the knee was performed according to the Kellgren-Lawrence grading system. Dkk-1 levels in both plasma and synovial fluid were evaluated using enzyme-linked immunosorbent assay., Results: The average concentration of circulating Dkk-1 in the knee OA patients was remarkably lower than that of healthy controls (396.0 ± 258.8, 95%CI 307.1-484.9 vs 2348.8 ± 2051.5, 95%CI 1164.3-3533.3 pg/ml, p < 0.0001). Dkk-1 levels in synovial fluid were significantly lower than in paired plasma samples (58.6 ± 31.8, 95%CI 47.7-69.6 vs 396.0 ± 258.8, 95%CI 307.1-484.9 pg/ml, p < 0.001). Furthermore, both plasma and synovial fluid Dkk-1 levels were inversely correlated with radiographic severity (r = -0.78, p < 0.001 and r = -0.42, p = 0.01, respectively). Plasma Dkk-1 levels were also significantly correlated with synovial fluid Dkk-1 levels (r = 0.72, p < 0.001)., Conclusions: Dkk-1 levels in plasma and synovial fluid are inversely related to the severity of joint damage in knee OA. Dkk-1 could serve as a biochemical marker for determining disease severity and might play a potential role in the pathogenesis of the degenerative process of OA.

Background and Aims: Osteoarthritis (OA) is a chronic degenerative joint disorder of the synovial joint characterized by loss of articular cartilage, osteophyte formation, and alterations of subchondral bone. The purposes of this study were to measure adiponectin concentrations in plasma and synovial fluid of patients with knee OA and to analyze the correlation of adiponectin levels with disease severity., Methods: Seventy six OA patients (mean age 69.8 ± 1.1 years) and 24 healthy controls (mean age 71.2 ± 1.5 years) were enrolled in this study. OA grading was performed using the Kellgren-Lawrence (KL) criteria by evaluating x-ray changes observed in anteroposterior knee radiography. Adiponectin levels in plasma and synovial fluid were determined by commercial enzyme-linked immunosorbent assay., Results: Plasma levels of adiponectin were higher in OA patients compared to healthy individuals, but the difference did not reach statistical significance (2428.0 ± 245.1 vs. 2030.3 ± 399.4 ng/mL, p = 0.4). Adiponectin levels in plasma were remarkably higher with regard to paired synovial fluid (2428.0 ± 245.1 vs. 301.3 ± 44.9 ng/mL, p <0.001). Additionally, adiponectin concentrations in plasma and synovial fluid showed significant inverse correlation with disease severity evaluated by KL grading criteria (r = -0.68, p <0.001 and r = -0.47, p <0.001, respectively). Further analysis showed that plasma adiponectin levels positively correlated with synovial fluid adiponectin levels (r = 0.71, p <0.001)., Conclusions: Adiponectin levels in both plasma and synovial fluid decreased significantly as the severity of OA increased. These findings suggested that adiponectin may play a protective role in OA. More studies are warranted to gain insight into the potential utility of adiponectin as a biochemical determinant of disease progression and prognosis., (Copyright © 2010 IMSS. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to measure soluble receptor for advanced glycation end products (sRAGE) in plasma and synovial fluid of knee osteoarthritis (OA) patients and to determine the correlation between sRAGE levels and disease severity., Design and Methods: Thirty-six OA patients and 15 healthy controls were enrolled in this study. OA grading was performed using the Kellgren-Lawrence classification. sRAGE levels in plasma and synovial fluid were analyzed by enzyme-linked immunosorbent assay., Results: Plasma sRAGE levels were significantly lower in OA patients than in healthy controls (P=0.01). sRAGE levels in plasma were remarkably higher with regard to paired synovial fluid (P=0.001). Additionally, sRAGE concentrations in plasma and synovial fluid showed significant inverse correlation with disease severity (r=-0.65, P<0.001 and r=-0.55, P=0.001, respectively). Further analysis showed that there was a strong positive correlation between plasma and synovial sRAGE concentration (r=0.81, P<0.001)., Conclusions: sRAGE levels were significantly lower in OA patients compared with controls, and sRAGE levels in plasma and synovial fluid also decreased significantly as the disease severity increased. Accordingly, sRAGE levels could be used as a biochemical marker for assessing the severity and progression of knee OA., (Copyright (c) 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Osteoarthritis (OA) is a chronic degenerative joint disorder of the synovial joint characterized by loss of articular cartilage, osteophyte formation, and alterations of subchondral bone. The aim of this study was to evaluate endoglin levels in both plasma and synovial fluid of patients with primary knee OA and to determine their relationship with disease severity., Methods: Thirty nine patients with primary knee OA and 15 healthy controls were recruited in this study. The radiographic grading of OA in the knee was performed using the Kellgren and Lawrence classification. Endoglin concentrations in both plasma and synovial fluid were analyzed using a sandwich enzyme-linked immunosorbent assay., Results: The average value of plasma endoglin in patients with knee OA was significantly higher compared with that of healthy controls (5.16+/-0.22 vs. 4.43+/-0.3 ng/mL, p=0.03). Although endoglin levels in synovial fluid were higher with respect to paired plasma samples, the difference was not significant (5.41+/-0.32 vs. 5.16+/-0.22 ng/mL, p=0.3). Additionally, plasma endoglin levels exhibited a positive correlation with synovial fluid endoglin levels (r=0.52, p=0.001). Further analysis revealed that plasma endoglin levels significantly correlated with disease severity (r=0.38, p=0.02). Furthermore, the synovial fluid levels of endoglin also positively correlated with disease severity (r=0.55, p=0.001)., Conclusions: These findings indicate that endoglin in plasma and synovial fluid is correlated with progressive joint damage in knee OA. Endoglin is likely to be useful as a biomarker for determining disease severity and may play a possible role in the pathogenesis of osteoarthritis., (2009 IMSS. Published by Elsevier Inc.)

The objective of this study was to investigate bone morphogenetic protein-7 (BMP-7) levels in both plasma and synovial fluid of patients with primary knee osteoarthritis (OA) and to determine their relationship to disease severity. Thirty-two patients with knee OA and 15 healthy subjects were enrolled in the study. Anteroposterior knee radiographs were taken to determine the disease severity of the affected knee. The radiographic grading of OA in the knee was performed using the Kellgren-Lawrence criteria. BMP-7 levels in the plasma and synovial fluid were measured using enzyme-linked immunosorbent assay. The mean plasma BMP-7 concentration of the knee OA patients was significantly higher compared with that of healthy controls (12.1 +/- 1.6 vs 3.5 +/- 0.9 pg/ml, P = 0.001). Although BMP-7 levels in plasma were higher with respect to paired synovial fluid samples, the difference was not statistically significant (12.1 +/- 1.6 vs 10.5 +/- 2.2 pg/ml, P = 0.3). Subsequent analysis showed that plasma BMP-7 levels significantly correlated with disease severity (r = 0.77, P < 0.001). Furthermore, the synovial fluid levels of BMP-7 also correlated with disease severity (r = 0.60, P < 0.001). In addition, plasma BMP-7 levels showed a positive correlation with synovial fluid BMP-7 levels (r = 0.71, P < 0.001). Overexpression of BMP-7 in plasma and synovial fluid is related to progressive joint damage in knee OA. These findings suggest that BMP-7 might serve as a biochemical parameter for determining disease severity in primary knee OA and could play a potential role in cartilage protection and repair of OA.

Objectives: The purposes of this study were to examine osteopontin levels in both plasma and synovial fluid of patients with primary knee osteoarthritis (OA) and to investigate their relationship with severity of the disease., Design and Methods: Thirty-two patients aged 53-83 years with knee OA and 15 healthy controls were enrolled in this study. Anteroposterior knee radiographs were taken to determine the disease severity of the affected knee. The radiographic grading of OA in the knee was performed by using the Kellgren-Lawrence criteria. Osteopontin levels in the plasma and synovial fluid were measured using enzyme-linked immunosorbent assay., Results: The mean plasma osteopontin concentration of the knee OA patients was significantly higher compared with that of healthy controls (168.8+/-15.6 vs 67.2+/-7.7 ng/mL, P<0.0001). Osteopontin levels in synovial fluid were significantly higher with respect to paired plasma samples (272.1+/-15.0 vs 168.8+/-15.6 ng/mL, P<0.001). In addition, plasma osteopontin levels showed a positive correlation with synovial fluid osteopontin levels (r=0.373, P=0.035). Subsequent analysis showed that plasma osteopontin levels significantly correlated with severity of disease (r=0.592, P<0.001). Furthermore, the synovial fluid levels of osteopontin also correlated with disease severity (r=0.451, P=0.01)., Conclusion: The data suggest that osteopontin in plasma and synovial fluid is related to progressive joint damage in knee OA. Osteopontin may serve as a biochemical marker for determining disease severity and could be predictive of prognosis with respect to the progression of knee OA.